Chlamydia pneumoniae is an intracellular bacterium which commonly causes respiratory infections. Chronic infections have been associated with atherosclerosis and the organism has been detected in macrophages in the disease lesions. Growth of chlamydiae in different epithelial cell lines is restricted by interferon-gamma (IFN-γ), a monocyte activator produced by T cells. We have studied the influence of IFN-γ on the growth and infectivity of C. pneumoniae in HL-cells and human monocyte-derived macrophages. Low concentrations of the cytokine significantly restricted the growth and productivity of C. pneumoniae in epithelial cells in vitro. In macrophages, however, no effect on the growth of the bacteria in infected cells was found, but high doses clearly restricted the production of infectious progeny. The results suggest that IFN-γ participates in the resistance to C. pneumoniae. The bacterium is, however, still capable of infecting macrophages that are important in the pathogenesis of atherosclerosis and it may thus participate in the inflammatory process associated with the disease.